POS1029 MACROPHAGE MARKERS FOLATE RECEPTOR BETA AND CD206 ARE DIFFERENTIALLY EXPRESSED IN SYNOVIAL TISSUE OF RA PATIENTS WITH A DIFFUSE-MYELOID, LYMPHO-MYELOID AND FIBROID-PAUCI IMMUNOPATHOTYPE
Authors: M. Steinz, J. Van der Krogt, J. P. Van Hamburg, G. Jansen, S. Tas, C. J. Van der Laken
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Three different synovial immunopathotypes of rheumatoid arthritis (RA) have been identified: Fibroid-Pauci immune (FP, fibroblast-rich), Diffuse-Myeloid (DM, macrophage-rich) and Lympho-Myeloid (LM, lymphocyte- and macrophage-rich), and have been associated with treatment outcome to biologicals [1]. Therefore, identification of the synovial immunopathotypes before the start of therapy could be supportive for development of individualized treatment strategies. However, this currently requires invasive synovial tissue sampling. Novel whole-body molecular imaging with positron emission tomography (PET) and the use of specific PET tracers can non-invasively detect and quantify the presence of immune cells in RA inflamed synovium. Folate-receptor beta (FRβ) is a cell surface receptor on macrophages, shown clinical exploitation for high specificity PET imaging of arthritis [2]. However, it remains to be elucidated whether FRβ is a suitable marker for RA immunopathotype stratification. Furthermore, it is unclear whether FRβ is expressed on macrophages with a pro-inflammatory (M1) or homeostatic (M2) phenotype in the 3 immunopathotypes. <h3>Objectives:</h3> (1) Investigate FRβ expression across the three distinct RA immunopathotypes. (2) Investigate FRβ expression in relation to the general macrophage marker CD68 and the mannose receptor CD206 (which is associated with M2-type macrophages [3]). <h3>Methods</h3> Synovial biopsies of the RA-affected ankle or knee (N=28) were retrieved from RA patients with clinically active disease defined by ACR RA criteria [4]. Subsequently, biopsy sections were immunohistologically stained in order to stratify each patient into one of three RA-immunopathotypes. Confocal microscopy was used to determine CD68, FRβ and CD206 expression (integrated density), and co-expression (comparing fold-change average expression) for all patients within each immunopathotype (N=8-10/ group). <h3>Results</h3> Out of 28 RA synovial biopsies 10 could be classified as FP, 9 DM and 9 LM immunopathotype. Average expression of CD68, FRβ and CD206 was significantly increased in the DM and LM compared to the FP immunopathotype (## <i>p</i>&lt;0.01). Quantitative CD68, FRβ and CD206 expression was highest in the DM immunopathotype. FRβ expression correlated significantly with CD206 expression in all three pathotypes (Spearman R<sub>FP</sub>= 0.67; R<sub>DM</sub>= 0.76; R<sub>LM</sub>= 0.49). On the contrary FRβ expression did not correlate with CD68 expression except in the DM pathotype (Spearman R<sub>DM</sub>= 0.46). <h3>Conclusion</h3> The results of this study put forward that FRβ is a potential target for delineation of RA immunopathotypes, to be explored for non-invasive molecular imaging stratification. Furthermore, investigation of FRβ expression has an additive value over CD68 since it can be used to distinguish the presence of M2 macrophages in the RA synovium specifically. <h3>References</h3> [1] Lewis et al., Cell Rep. 2019;28(9):2455-2470.e5 [2] Steinz et al., Front Immunol. 2022;13:819163 [3] Alivernini et al., Nat. Med. 2020;26(8):1295-1306 [4] Arnet et al., Arthritis Rheum. 1988;31(3):315-24 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.